1. Field of the Invention
The present invention relates to a process for the fermentative production of a dicarboxylic acid by yeast and the recovery of the dicarboxylic acid by crystallization.
2. Description of Related Art
Dicarboxylic acids such as malic acid, fumaric acid and succinic acid, are important compounds which are used in the food industry for the preparation and preservation of food, in the medical industry for the formulation of medical products, building blocks in (bio)polymers and other industrial uses. To meet the increasing need for dicarboxylic acids, more efficient and cost effective production methods are being developed.
Bacteria can produce large amounts of dicarboxylic acids. However, one major drawback associated with the use of bacteria for producing dicarboxylic acids is the formation of the acid salt. If bacteria are used, the pH needs to be maintained in the range of pH 6-7. As a consequence, most acids will be produced in their salt form and the salts will have to be converted into the acid. This is not practical or efficient in large-scale production processes and raises production costs. Alternatively, low pH processes are considered to be more attractive, in particular at a large scale.
Yeasts are attractive candidates for low pH dicarboxylic acid production processes. However, at low pH a dicarboxylic acid in the acid form diffuses through the cell membrane inside the cell, whereupon the cell will try to transport the dicarboxylic acid outside the cell. This transport will likely require energy in the form of ATP. Under aerobic conditions, a yeast cell can generate energy in the form of ATP by oxidative respiration. An aerobic process for the production of malic acid and succinic acid by a (genetically modified) yeast is for instance disclosed in WO2007/061590. However, aerobic processes for the production of dicarboxylic acid by yeast fermentation are not desirable since under aerobic conditions the dicarboxylic acid yield on carbon is estimated to be lower than under anaerobic conditions.
Under anaerobic conditions, yeast produces dicarboxylic acid via the reductive tricarboxylic acid cycle, producing 1 mole of ATP, which is considered not to be sufficient for maintenance of the cell and/or transport of the dicarboxylic acid outside the cell. Therefore, the yeast cell will need to use alternative ways to generate energy during anaerobic dicarboxylic acid fermentation, with little to no expense of the dicarboxylic acid yield.